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Fluctuations in temperature are recognized as a potent driver of selection pressure, fostering genomic variations that are crucial for the adaptation and survival of organisms under selection. Notably, water temperature is a pivotal factor influencing aquatic organism persistence. By comprehending how aquatic organisms respond to shifts in water temperature, we can understand their potential physiological adaptations to environmental change in one or multiple species. This, in turn, contributes to the formulation of biologically relevant guidelines for the landscape scale transcriptome profile of organisms in lotic systems. Here, we investigated the distinct responses of seven stream stonefly species, collected from four geographical regions across Japan, to variations in temperature, including atmospheric and water temperatures. We achieved this by assessing the differences in gene expression through RNA-sequencing within individual species and exploring the patterns of community-genes among different species. We identified 735 genes that exhibited differential expressions across the temperature gradient. Remarkably, the community displayed expression levels differences of respiration and metabolic genes. Additionally, the diversity in molecular functions appeared to be linked to spatial variation, with water temperature differences potentially contributing to the overall functional diversity of genes. We found 22 community-genes with consistent expression patterns among species in response to water temperature variations. These genes related to respiration, metabolism and development exhibited a clear gradient providing robust evidence of divergent adaptive responses to water temperature. Our findings underscore the differential adaptation of stonefly species to local environmental conditions, suggesting that shared responses in gene expression may occur across multiple species under similar environmental conditions. This study emphasizes the significance of considering various species when assessing the impacts of environmental changes on aquatic insect communities and understanding potential mechanisms to cope with such changes., (© 2024 Wiley Periodicals LLC.)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are now a public health concern in both community and healthcare settings worldwide. We previously identified a suspected case of a maternity clinic-centred outbreak of CA-MRSA skin infection in a regional community in Japan by PFGE-based analysis. In this study, we performed genome sequence-based analyses of 151 CA-MRSA isolates, which included not only outbreak-related isolates that we previously defined based on identical or similar PFGE patterns but also other isolates obtained during the same period in the same region. Our analysis accurately defined 133 isolates as outbreak-related isolates, collectively called the TDC clone. They belonged to a CA-MRSA lineage in clonal complex (CC) 30, known as the South West Pacific (SWP) clone. A high-resolution phylogenetic analysis of these isolates combined with their epidemiological data revealed that the TDC clone was already present and circulating in the region before the outbreak was recognized, and only the isolates belonging to two sublineages (named SL4 and SL5) were directly involved in the outbreak. Long persistence in patients/carriers and frequent intrahousehold transmission of the TDC clone were also revealed by this analysis. Moreover, by systematic analyses of the genome changes that occurred in this CA-MRSA clone during transmission in the community, we revealed that most variations were associated with mobile genetic elements (MGEs). Variant PFGE types were generated by alterations of prophages and genomic islands or insertion sequence (IS)-mediated insertion of a plasmid or a sequence of unknown origin. Dynamic changes in plasmid content, which were linked to changes in antimicrobial resistance profiles in specific isolates, were generated by frequent gain and loss of plasmids, most of which were self-transmissible or mobilizable. The introduction of IS 256 by a plasmid (named pTDC02) into sublineage SL5 led to SL5-specific amplification of IS 256, and amplified IS 256 copies were involved in some of the structural changes of chromosomes and plasmids and generated variations in the repertoire of virulence-related genes in limited isolates. These data revealed how CA-MRSA genomes change during transmission in the community and how MGEs are involved in this process.

Background: Reference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established., Methods: This was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children's Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda-mu-sigma (LMS) method and compared with those obtained via the polynomial regression model., Results: Data from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively., Conclusion: The reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available., (© 2023. The Author(s).)

Background: Patient survival and physical outcomes among children with end-stage kidney disease (ESKD) have significantly improved, and recent research has focused on long-term depression symptoms and health-related quality of life (HRQOL). However, no studies have been conducted among adolescents and young adults with childhood-onset ESKD in Japan., Methods: This multicenter study included 45 adolescents and young adults aged 16-39 years who developed ESKD at age < 20 years. Depression symptoms were measured using the Beck Depression Inventory (BDI)-II. The Short Form-36 Health Survey (SF-36) was used to assess HRQOL. Factors associated with depression and HRQOL were analyzed., Results: Depression (BDI-II score ≥ 14) was observed in 13 (29%) patients. Patient's SF-36 physical component summary (PCS) and mental component summary (MCS) scores were comparable with those for the general population. Lower estimated glomerular filtration rate, higher BDI-II scores, and lower body mass index were associated with lower PCS scores. BDI-II scores were negatively correlated with MCS scores. We observed a trend that unemployment was associated with lower MCS scores., Conclusions: Depression is frequently observed among adolescents and young adults with childhood-onset ESKD. Regular screening for psychosocial concerns, maintaining stable graft functions, and achieving optimal nutritional status may contribute to improved well-being among these patients., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Adolescents and young adults face various socio-emotional and behavioral challenges that can affect their medical and psychosocial outcomes. Pediatric patients with end-stage kidney disease (ESKD) often have extra-renal manifestations, including intellectual disability. However, limited data are available regarding the impact of extra-renal manifestations on medical and psychosocial outcomes among adolescents and young adults with childhood-onset ESKD., Methods: Patients born between January 1982 and December 2006 that had developed ESKD in 2000 and later at age < 20 years were enrolled in this multicenter study in Japan. Data for patients' medical and psychosocial outcomes were retrospectively collected. Associations between extra-renal manifestations and these outcomes were analyzed., Results: In total, 196 patients were analyzed. The mean age at ESKD was 10.8 years, and at last follow-up was 23.5 years. The first modality of kidney replacement therapy was kidney transplantation, peritoneal dialysis, and hemodialysis in 42, 55 and 3% of patients, respectively. Extra-renal manifestations were documented in 63% of patients and 27% had intellectual disability. Baseline height at kidney transplantation and intellectual disability significantly impacted final height. Six (3.1%) patients died, of which five (83%) had extra-renal manifestations. Patients' employment rate was lower than that in the general population, especially among those with extra-renal manifestations. Patients with intellectual disability were less likely to be transferred to adult care., Conclusions: Extra-renal manifestations and intellectual disability in adolescents and young adults with ESKD had considerable impacts on linear growth, mortality, employment, and transfer to adult care., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Objective: Elizabethkingia anophelis causes meningitis, bloodstream infections, and respiratory infections in immunocompromised individuals. We examined two E. anophelis strains isolated from the first life-threatening cases caused by this species in Japan to determine the phylogenetic origin and genomic features of them., Methods: We performed whole genome-based analysis to clarify the genetic relationship for the two strains (EK0004 and EK0079) and Elizabethkingia sp. strains isolated from worldwide and to characterize the genomic features such as the prevalence of virulence- and antimicrobial resistance (AMR)-related genes., Patients: A 29-year-old man with hepatosplenic T-cell lymphoma and a 52-year-old man with systemic lupus erythematosus developed fatal bacteremia and meningitis due to E. anophelis, respectively., Results: Two strains, EK0004 and EK0079, were genetically different but most closely related to the strains isolated from the largest outbreak in Wisconsin, USA from 2015 to 2016, and the strain isolated from cerebrospinal fluid of a patient in Florida, USA in 1982, respectively. The two strains contained AMR-related genes such as those encoding for an extended-spectrum β-lactamase and multiple metallo-β-lactamases and several virulence-related genes such as capsular polysaccharide synthesis gene clusters., Conclusions: Although further functional analyses are required to understand the virulence of these clones, these finding suggests that enough caution of E. anophelis infection in immunocompromised patients is required since the number of infections by this species is increasing outside Japan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants., Methods: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis., Results: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]"., Conclusion: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established., (© 2022. The Author(s).)

Background: Little is known about the epidemiology of Henoch-Schönlein purpura nephritis (HSPN)., Methods: We conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols., Results: A total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved., Conclusions: The incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis., Competing Interests: RH received research funding from Teijin Pharma Ltd. and was a stockholder in Mitsubishi Tanabe Pharma Co.. IT received research funding from Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co. Ltd., Bayer Yakuhin, Ltd., and Sunny Health Co., Ltd. and lecture fees from Takeda Pharmaceutical Co., Ltd. and Novartis Pharma K.K.. KI received research funding from Zenyaku Kogyo Co. Ltd. and subsidies or donations from Daiichi Sankyo Co. Ltd.. SI received research funding form Teijin Pharma, Ltd. and lecture fees from Sanofi K.K. and Alexion Pharmaceuticals Inc. The other authors have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. None of the research funding received by individual researchers mentioned in the Competing Interests statement are relate to this current study.

Background: We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFR Uemura ). The eGFR equation is for children aged 2-18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFR under 2 ). The aim of the present study was to validate this new equation., Methods: We collected the data of 13 patients from previous studies and compared the results of eGFR under 2 , eGFR Uemura , and updated eGFR developed by Schwartz (eGFR Schwartz ) with measured GFR using mean error (ME), root mean square error (RMSE), P 30 and Bland-Altman analysis., Results: The ME of eGFR under 2 , eGFR Uemura and eGFR Schwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m 2 , respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P 30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland-Altman bias analysis showed fan-shape. The eGFR under 2 equation was the most accurate in the three equations., Conclusion: The eGFR under 2 equation was useful for Japanese children younger than 2 years., (© 2021. The Author(s).)

Background: There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients., Methods: Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m 2  × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin)., Results: Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study., Conclusions: The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. CLINICALTRIALS., Gov Identifier: NCT03345316., (© 2021. The Author(s).)

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN., Competing Interests: The authors have declared that no competing interests exist.

Background: Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR?, Methods: This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution., Results: The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m 2 at last encounter. Pathway analyses showed intrauterine malnutrition (β = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (β = - 0.19) and prematurity (β = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period., Conclusions: IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

Background: Information on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce., Methods: The Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients' prognosis in this cohort., Results: We obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8-9.4] and a median follow-up period of 4.1 years (IQR 2.5-5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin <1.0 g/dL) and severe bacterial infection were not independent factors, but female sex {hazard ratio [HR] 1.5 [95% confidence interval (CI) 1.1-1.7]} and hypertension [HR 4.0 (95% CI 2.6-6.0)] were significantly related to AKI. During the observation period, ocular hypertension requiring treatment occurred in 17.4% of patients, among which 0.4% received surgical treatment. Progression to frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome in 3 years was seen in 44.2% of the patients and was shown by the Cox regression analysis to be significantly related to younger age and days until remission at the first episode, but not to sex, hematuria, the minimum serum albumin level or AKI. Two patients died during the observation period. One patient showed progression to end-stage kidney disease., Conclusion: Based on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aim: This study aimed to investigate the current progression status from screening phase to further investigation phase in the Japanese school urine mass screening (SUS) project., Methods: This retrospective cohort study on the SUS project across the Shiga Prefecture during 2012 to 2017 analysed data from school life instruction sheets, which are principal documents in the SUS project, regarding urinalysis, attendance at follow-up and diagnoses., Results: Between the years 2012 to 2017, a median of 107 out of 83 749 elementary school students (aged 6-11 years) and 215 out of 42 870 junior high students (aged 12-14 years) had urine abnormalities identified for the first time in the SUS project. Among those with urine abnormalities, a mean of 4.2% of elementary school and 1.8% of junior high school students, respectively, were diagnosed with suspected glomerulonephritis for the first time. Overall, 5.9% (95% confidence interval [CI] 4.1, 7.7) and 23.6% (95% CI 21.3, 25.9) of proteinuria-positive elementary and junior high school students, respectively, did not undergo further investigations. The probability of a student undergoing further investigations was not affected by the local availability of medical care benefits., Conclusion: In the current SUS project, screening frequently does not lead to further investigation, especially among junior high school students. To maintain the integrity of the SUS project and to prevent the progression of renal disease in young students, efforts including elucidation of barriers to further investigations should be made to reduce the proportions of students not undergoing further investigations for abnormal urinalysis findings., (© 2020 Asian Pacific Society of Nephrology.)

Background: Cytomegalovirus (CMV) infection is one of the major factors that affect morbidity and mortality in kidney transplant (KTx) patients. The rate of CMV seropositivity in children before KTx is lower than that in adults; therefore, pediatric KTx patients have a higher risk of CMV infection. In Japanese pediatric KTx patients, preemptive therapy for CMV infection is a main conventional therapy. This study investigated whether this preemptive treatment would affect kidney function at 2 years post-KTx., Methods: A total of 163 patients, that is approximately half of the Japanese pediatric KTx patients nationwide, were recruited to participate in our study. We compared the values of the sequential estimated glomerular filtration rate (eGFR) at two years post-KTx and other influencing factors in CMV viremia, CMV disease, and no-infection groups., Results: Cytomegalovirus infection after KTx occurred in 75 patients (46.0%), 38.7% of whom developed CMV disease. The sequential eGFR values post-KTx did not differ significantly between the three groups. CMV infection was not significantly correlated with other factors, other infections (including Epstein-Barr [EB] virus infection), acute rejection (AR), or adverse events. Only prolonged duration of total hospitalization was significantly associated with CMV infection (P = .002). In the multivariate analysis, younger age, CMV infection, and adverse effects were independently significantly related to prolonged total hospitalization., Conclusion: Preemptive therapy for CMV infection evidenced by viremia and disease did not significantly influence kidney function in Japanese pediatric KTx patients at two years after the operation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma., Methods: A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed., Results: A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22., Conclusions: The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

The objectives of this study were to estimate the heritability of mastitis incidence and genetic correlations between the mastitis and the somatic cell score (SCS) statistics, and to compare the practicability between different models. We used test-day records with the mastitis incidence and SCS collected from Holstein cows calving from 1988 to 2015 in Hokkaido, Japan. As indicators of mastitis, the average SCS (avSCS), the standard deviation of SCS (sdSCS), and the maximum SCS (maxSCS) were calculated using test-day records up to the first 305 days in milk within a lactation. We compared a four-trait repeatability animal model (MTRP) with a four-trait multiple-lactation animal model (MTML). The heritability for mastitis was equal to or lower than 0.05 in all the models. Genetic correlations between lactations with MTML within the same trait were positive and close to 1. With MTRP, the estimated genetic correlations of the mastitis incidence with avSCS, sdSCS, and maxSCS were 0.66, 0.79, and 0.82, respectively. A joint evaluation with SCS statistics is expected to give an extra reliability for mastitis because of high and positive genetic correlations among the traits., (© 2019 Japanese Society of Animal Science.)

Helicobacter cinaedi is an emerging pathogen causing bacteraemia and cellulitis. Nosocomial transmission of this microbe has been described, but detailed molecular-epidemiological analyses have not been performed. Here, we describe the results of a multi-step genome-wide phylogenetic analysis of a suspected intra-hospital outbreak of H. cinaedi that occurred in a hospital in Japan. The outbreak was recognized by the infectious control team (ICT) of the hospital as a sudden increase in H. cinaedi bacteraemia. ICT defined this outbreak case based on 16S rRNA sequence data and epidemiological information, but were unable to determine the source and route of the infections. We therefore re-investigated this case using whole-genome sequencing (WGS). We first performed a species-wide analysis using publicly available genome sequences to understand the level of genomic diversity of this under-studied species. The clusters identified were then separately analysed using the genome sequence of a representative strain in each cluster as a reference. These analyses provided a high-level phylogenetic resolution of each cluster, identified a confident set of outbreak isolates, and discriminated them from other closely related but distinct clones, which were locally circulating and invaded the hospital during the same period. By considering the epidemiological data, possible strain transmission chains were inferred, which highlighted the role of asymptomatic carriers or environmental contamination. The emergence of a subclone with increased resistance to fluoroquinolones in the outbreak was also recognized. Our results demonstrate the impact of the use of a closely related genome as a reference to maximize the power of WGS.

Background: Several factors affect the level of difficulty of laparoscopic distal pancreatectomy (LDP). The purpose of this study was to develop a difficulty scoring (DS) system to quantify the degree of difficulty in LDP., Methods: We collected clinical data for 80 patients who underwent LDP. A 10-level difficulty index was developed and subcategorized into a three-level difficulty index; 1-3 as low, 4-6 as intermediate, and 7-10 as high index. The automatic linear modeling (LINEAR) statistical tool was used to identify factors that significantly increase level of difficulty in LDP., Results: The operator's 10-level DS concordance between the 10-level DS by the reviewers, LINEAR index DS, and clinical index DS systems were analyzed, and the weighted Cohen's kappa statistic were at 0.869, 0.729, and 0.648, respectively, showing good to excellent inter-rater agreement. We identified five factors significantly affecting level of difficulty in LDP; type of operation, resection line, proximity of tumor to major vessel, tumor extension to peripancreatic tissue, and left-sided portal hypertension/splenomegaly., Conclusions: This novel DS for LDP adequately quantified the degree of difficulty, and can be useful for selecting patients for LDP, in conjunction with fitness for surgery and prognosis., (© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The gold standard for evaluation of kidney function is renal inulin clearance (Cin). However, the methodology for Cin is complicated and difficult, especially for younger children and/or patients with bladder dysfunction. Therefore, we developed a simple and easier method for obtaining the estimated glomerular filtration rate (eGFR) using equations and values for several biomarkers, i.e., serum creatinine (Cr), serum cystatin C (cystC), serum beta-2 microglobulin (β 2 MG), and creatinine clearance (Ccr). The purpose of the present study was to validate these equations with a new data set., Methods: To validate each equation, we used data of 140 patients with CKD with clinical need for Cin, using the measured GFR (mGFR). We compared the results for each eGFR equation with the mGFR using mean error (ME), root mean square error (RMSE), P 30 , and Bland-Altman analysis., Results: The ME of Cr, cystC, β 2 MG, and Ccr based on eGFR was 15.8 ± 13.0, 17.2 ± 16.5, 15.4 ± 14.3, and 10.6 ± 13.0 ml/min/1.73 m 2 , respectively. The RMSE was 29.5, 23.8, 20.9, and 16.7, respectively. The P 30 was 79.4, 71.1, 69.5, and 92.9%, respectively. The Bland-Altman bias analysis showed values of 4.0 ± 18.6, 5.3 ± 16.8, 12.7 ± 17.0, and 2.5 ± 17.2 ml/min/1.73 m 2 , respectively, for these parameters., Conclusion: The bias of each eGFR equation was not large. Therefore, each eGFR equation could be used.

Background: End-stage renal disease (ESRD) in children is considered a rare, but serious condition. Epidemiological and demographic information on pediatric ESRD patients around the world is important to better understand this disease and to improve patient care. The Japanese Society for Pediatric Nephrology (JSPN) reported epidemiological and demographic data in 1998. Since then, however, there has been no nationwide survey on Japanese children with ESRD., Methods: The JSPN conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011., Results: The average incidence of ESRD was 4.0 per million age-related population. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2 % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis. Initial treatment modalities in patients who commenced renal replacement therapy (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT mortality rate was 18.2 deaths per 1000 person-years of observation., Conclusion: The incidence of ESRD is lower in Japanese children than in children of other high-income countries. Since 1998, notably, there has been a marked increase in pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.

Background: The present study was performed to determine the reference values of glomerular filtration rate (GFR) in children by age using the new eGFR equations derived from serum creatinine (Cr) and cystatine C (cysC)., Methods: A total of 1137 children (509 males and 628 females) between the ages of 3 months and 16 years presenting at our facilities between 2008 and 2009 without diseases affecting the renal function were included in this study as in our previous reports for reference values of serum Cr and cysC. We calculated eGFR with the Cr based equation in children aged 2-16 years, and with the cysC based equation in those aged 3-23 months, and determined the reference values of GFR in Japanese children by each age group., Results: We reviewed the median, 2.5 and 97.5 percentile of GFR reference value in each age group. The medians of reference GFRs are 91.7, 98.5, 106.3, and 113.1 mL/min/1.73 m(2) in children aged 3-5, 6-11, 12-17, and 18 months-16 years, respectively., Conclusion: We determined the normal reference values of GFR in children. It is important for pediatricians who examine pediatric chronic kidney disease patients to know the values of normal renal function.

Objectives: The aim of the present study was to assess the appropriate administration dose of non-steroidal anti-inflammation drugs to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Importantly, the 100 mg dose of diclofenac recommended in Western countries has not been permitted in Japan., Design: A retrospective study., Settings: A single centre in Japan., Participants: This study enrolled patients who underwent ERCP at the Department of Gastroenterology, Osaka Saiseikai Senri Hospital, from April 2011 through June 2013, and who received either a 25 or a 50 mg dose of rectal diclofenac after ERCP., Primary Outcome Measure: The occurrence of post-ERCP pancreatitis (PEP). A multivariate regression model was used to assess the effect of the 50 mg dose (the 50 mg group) of rectal diclofenac and to compare it to the occurrence of PEP referring to the 25 mg group., Results: A total of 155 eligible patients received either 25 mg (84 patients) or 50 mg (71 patients) doses of rectal diclofenac after ERCP to prevent PEP. The proportion of PEP was significantly lower in the 50 mg group than in the 25 mg group (15.5% (11/71) vs 33.3% (28/84), p=0.018). In a multivariate analysis, the occurrence of PEP was significantly lower in the 50 mg group than in the 25 mg group even after adjusting potential confounding factors (adjusted OR=0.27, 95% CI 0.11 to 0.70)., Conclusions: From this observation, the occurrence of PEP was significantly lower among ERCP patients with the 50 mg dose of rectal diclofenac than among those with the 25 mg dose., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: We evaluated the safety and efficacy of darbepoetin alfa (DA), an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia, in Japanese children with chronic kidney disease (CKD) on peritoneal dialysis (PD) and hemodialysis (HD), and not on dialysis (ND)., Methods: A total of 31 pediatric CKD patients (13 PD, 2 HD, and 16 ND) were enrolled. DA was administered bi-weekly intravenously (IV) or subcutaneously (SC) for PD or ND patients, and weekly IV for HD patients for 24 weeks. The target Hb was defined as 11.0 to ≤13.0 g/dl. In patients receiving rHuEPO, the initial DA dose was calculated at 1 μg DA for 200 IU rHuEPO. The initial DA dose for naïve patients was determined by body weight, and intended not to exceed 0.5 μg/kg per administration. For some PD or ND patients, the dosing frequency was subsequently changed to once every 4 weeks., Results: Mean Hb values increased from 10.5 ± 1.1 to 11.1 ± 1.1 g/dl after 4 weeks of DA treatment. The target Hb was achieved in all patients, 64.5 % of whom maintained the value at completion of the study. Hb responses were similar between IV and SC. The dosing frequency was extended to once every 4 weeks in 37.9 % of PD or ND patients. Eighty-seven adverse events were noted in 27 (87.1 %) of 31 patients, none of which were associated with DA., Conclusion: These results suggest that IV or SC administration of DA is an effective and safe treatment for renal anemia in Japanese children with CKD.

Background: Renal inulin clearance is the gold standard for evaluation of kidney function, but cannot be measured easily in children. Therefore, we utilize the serum creatinine (Cr)-based estimated GFR (eGFR) measuring serum Cr by the enzymatic method, and we have reported simple serum Cr-based eGFR in Japanese children aged between 2 and 11 years old. Furthermore, we should use serum Cr-based eGFR in Japanese adolescents as well as children with chronic kidney disease for evaluation of renal function., Methods: The inulin clearance and serum Cr level determined by an enzymatic method were measured in 131 pediatric chronic kidney disease (CKD) patients between the ages of 2 and 18 years old with no underlying disease affecting renal function except CKD to determine the serum Cr-based eGFR in Japanese children and adolescents., Results: We offer the complex estimated GFR equation using polynomial formulae for reference serum creatinine levels with body length in Japanese children except infants, resulting in the following equation:[Formula: see text] Reference serum Cr levels (y) are shown by the following two equations of body length (x):[Formula: see text], Conclusion: The new polynomial eGFR formula showing the relationship with body length and serum Cr level may be applicable for clinical screening of renal function in Japanese children and adolescents aged between 2 and 18 years.

As Japan's industries pursue technical innovations, the responsibilities of occupational health nurses are becoming increasingly complex. With such change, continuing professional development (CPD) and continuing education (CE) are crucial to the provision of appropriate care for workers. This study examined current practices of occupational health nurses and identified barriers to conducting occupational CPD and CE activities. A survey questionnaire was sent to 2,077 occupational health nurses late in 2010, asking about factors affecting attendance at and participation in CPD and CE activities, including challenges for occupational health nurses in practice. Findings demonstrated that many occupational health nurses do not work for companies that support CPD and CE. A significant finding was that occupational health nurses in Japan desire CPD activities and recognize the importance of attending CE activities. Continuing education is viewed by occupational health nurses as essential for their professional development and advancement with broader practice responsibilities and authority. Findings from this study are useful in crafting recommendations to increase occupational health nurse participation in both CPD and CE, leading to improvement in overall workplace health and safety in Japan., (Copyright 2014, SLACK Incorporated.)

The aim of this study was to estimate genetic correlations between milk yield, somatic cell score (SCS), mastitis, and claw and leg disorders (CLDs) during first lactation in Holstein cows by using a threshold-linear random regression test-day model. We used daily records of milk, fat and protein yields; somatic cell count (SCC); and mastitis and CLD incidences from 46 771 first-lactation Holstein cows in Hokkaido, Japan, that calved between 2000 and 2009. A threshold animal model for binary records (mastitis and CLDs) and linear animal model for yield traits were applied in our multiple trait analysis. For both liabilities and yield traits, additive genetic effects were used as random regression on cubic Legendre polynomials of days on milk. The highest positive genetic correlations between yields and disease incidences (0.36 for milk and mastitis, 0.56 for fat and mastitis, 0.24 for protein and mastitis, 0.32 for milk and CLD, 0.44 for fat and CLD and 0.31 for protein and CLD) were estimated at about the time of peak milk yield (36 to 65 days in milk). Selection focused on early lactation yield may therefore increase the risk of mastitis and CLDs. The positive genetic correlations of SCS with mastitis or CLD incidence imply that selection to reduce SCS in the early stages of lactation would decrease the incidence of both mastitis and CLD.

Purpose: To report the ophthalmic relief activities conducted by Iwate Medical University after the Great East Japan Earthquake of March 11, 2011., Subjects and Methods: A retrospective review was conducted of the medical records of patients who visited emergency ophthalmic clinics opened at Yamada-cho, Otsuchi-cho and Rikuzentakada-shi from March 30, 2011 to June 30, 2011., Results: We provided ophthalmic medical care for 14 days at Yamada-cho and Otsuchi-cho, and for 9 days at Rikuzentakada-shi. During this period, 1371 new patients (total of 2015 patients) visited the clinics. The main motives were a desire for prescription of medication, treatment of ocular symptoms and correction of refractive error and presbyopia. The major diseases were cataract, pseudophakia, refractive error, presbyopia and conjunctivitis. Only a few patients had a foreign body in the eye or ocular trauma. Among the 207 patients with contact lenses, 24 patients were wearing them beyond their replacement date, and contact lens care was insufficient in 35 patients. Among 179 patients with glaucoma who were checked for intraocular pressure, 61 patients had an IOP greater than 21 mmHg., Conclusions: Although many patients sought eye drops for chronic eye diseases and correction of refractive error and presbyopia, patients with ocular injuries were few. It is important to prepare for whatever needs patients in emergency circumstances may present.

We investigated the relationships between conception rates (CRs) at first service in Japanese Holstein heifers (i.e. animals that had not yet had their first calf) and cows and their test-day (TD) milk yields. Data included records of artificial insemination (AI) for heifers and cows that had calved for the first time between 2000 and 2008 and their TD milk yields at 6 through 305 days in milk (DIM) from first through third lactations. CR was defined as a binary trait for which first AI was a failure or success. A threshold-linear animal model was applied to estimate genetic correlations between CRs of heifers or cows and TD milk yield at various lactation stages. Two-trait genetic analyses were performed for every combination of CR and TD milk yield by using the Bayesian method with Gibbs sampling. The posterior means of the heritabilities of CR were 0.031 for heifers, 0.034 for first-lactation cows and 0.028 for second-lactation cows. Heritabilities for TD milk yield increased from 0.324 to 0.433 with increasing DIM but decreased slightly after 210 DIM during first lactation. These heritabilities from the second and third lactations were higher during late stages of lactation than during early stages. Posterior means of the genetic correlations between heifer CR and all TD yields were positive (range, 0.082 to 0.287), but those between CR of cows and milk yields during first or second lactation were negative (range, -0.121 to -0.250). Therefore, during every stage of lactation, selection in the direction of increasing milk yield may reduce CR in cows. The genetic relationships between CR and lactation curve shape were quite weak, because the genetic correlations between CR and TD milk yield were constant during the lactation period.

Bepridil hydrochloride is used for treatment of atrial fibrillation (AF) in Japan. We investigated the relationship between plasma concentrations of bepridil just before dosing (Cbep) and its clinical efficacy in Japanese patients (n=36) with AF. Patients were treated orally with 100, 150 or 200 mg/d bepridil. Cbep were measured with UV-HPLC. In the first 14 d, when 150, 200, 250 or 300 ng/mL was set as a boundary value, the efficacy of bepridil was significantly higher in all patients with Cbep above than below the boundary value (p<0.05). In the maintenance stage (3 months longer after starting therapy), the efficacy of bepridil was significantly higher in patients with Cbep above than below 300 ng/mL (p=0.04). The clinical efficacy of bepridil was closely related to Cbep. The target value of Cbep to obtain a clinical benefit was approximately 300 ng/mL. Monitoring Cbep should be useful in the treatment of patients with AF.

We determined the urinary soluble tumor necrosis factor-α receptor type I (sTNFRI) and type II (sTNFRII) levels in healthy Japanese individuals to establish a reference value by means of specific ELISA. It was found that there were no significant differences between the urine sTNFRI and sTNFRII levels of children and adults. To demonstrate the usefulness of the reference value for children, we measured the urine sTNFRI and sTNFRII levels of children with diarrhea positive (D+) hemolytic uremic syndrome (HUS) as a preliminary study. The urine sTNFRI and sTNFRII levels of the patients with HUS were markedly higher than those of healthy children from the onset of D + HUS. Our reliable reference value for healthy children will allow us to discriminate between normal and pathological conditions in future studies.

An adult female white-tailed sea eagle (Haliaeetus albicilla), over 12 years old, was found moribund and sent to the Wildlife Rescue Center in Kushiro, Japan. Grossly, the bird had multifocal yellow to black nodules in the beak, tongue, mucosa of the oral cavity, eyelids, and legs. Histologically, the cutaneous nodules revealed severe epidermal hyperplasia. The thickened epithelium, from prickle cell layer to horny layer, consisted of swollen keratinocytes containing frequent eosinophilic intra-cytoplasmic inclusions, Bollinger bodies. Ultrastructurally, the epidermal cells had cytoplasmic viral particles with characteristics of poxvirus. Furthermore, the 4b core gene sequence of an avian poxvirus was detected in a DNA sample prepared from the nodular lesions by polymerase chain reaction. The nucleotide sequence of the polymerase chain reaction product showed 78 to 95% similarities to the sequences of other avian poxviruses. Phylogenetic analysis showed that the sequence is clustered in clade A but distant from all the subclades previously reported. The results imply that it is a novel avian poxvirus. To our knowledge this is the first report of avian poxvirus infection in white-tailed sea eagles.

We determined the serum basic fibroblast growth factor (bFGF) levels in healthy Japanese individuals to establish a reference value by means of specific human bFGF ELISA. It was found that there were no significant differences between the serum bFGF levels of children and adults. However, the reference value for children had a broader range than that of adults. Therefore, it is recommended that when the serum bFGF levels of patients are evaluated, the values should be compared with those of age-matched controls. To demonstrate the usefulness of the reference value for children, we measured the bFGF level of an 8-year boy with diarrhea positive (D+) hemolytic uremic syndrome (HUS), as a preliminary study. The serum bFGF level of the patient with HUS was markedly higher than those of healthy children from the onset of D+HUS. Our reliable reference value for healthy children will allow us to discriminate between normal and pathological conditions in future studies.

The levels of several soluble cytokine receptors in body fluids of healthy individuals change with age. Clinical application of the measurement of the serum soluble interleukin-1 receptor type I (sIL-1RI) level depends critically on the samples used as the controls. At present, there is no information regarding the levels of serum sIL-1RI in healthy subjects. The purpose of this study is to reveal the age-related changes that occur in the serum sIL-1RIlevels of healthy individuals. We determined the serum sIL-1RI levels of healthy Japanese children using ELISA. The serum sIL-1RI level of children (0-14 years) was significantly higher than that of adults (more than 15 years) (P = 0.0138, n = 90). Thus, it is recommended that when the serum sIL-1RI level of patients is evaluated, it should be compared against age-matched controls., (Copyright 2009 Wiley-Liss, Inc.)

Background: There are few published reports on kidney transplantation (KT) in physically handicapped patients with mental retardation. The aim of this study is to clearly identify the outcome of KT in these patients and clarify whether handicapped patients can be candidates for KT., Methods: Our study identified 25 multiply handicapped transplant recipients from 8 institutions. Causes of mental retardation were chromosomal abnormality in 5 patients, genetic syndrome in 10 patients, developmental brain anomaly in 2 patients, and other or unknown causes in 8 patients. Primary diseases leading to end-stage renal disease were congenital urinary tract anomaly in 12 patients, focal segmental glomerulosclerosis in 3 patients, cystic kidney disease in 3 patients, and other in 7 patients., Results: Twenty-three patients received living-related transplants from a parent and 2 patients received cadaver transplants. Twenty-two patients were on peritoneal dialysis therapy, 2 patients were on hemodialysis therapy at the time of KT, and 1 patient underwent preemptive KT. Eleven acute rejection episodes occurred in 8 patients. All episodes were completely reversed with treatments that included mainly methylprednisolone pulse therapy. Posttransplantation lymphoproliferative disorder occurred in 2 patients. Follow-up data showed that all grafts were functioning during a mean observation period of 41.1 months (range, 4 to 187 months). All persons providing primary support for patients were satisfied with the KT and believed that quality of life was improved in both transplant recipients and themselves., Conclusion: Results indicate that KT is not contraindicated in handicapped patients, but cannot determine which patients are unsuitable to undergo KT.

The genetic polymorphism of transferrin (TF) was studied in 2,167 Japanese individuals and in 448 New Zealanders. The three TF C subtypes were identified, but TF C3 was absent from Japanese populations. In addition, three TF B and six TF D variants were observed, each of which occurred either in Japanese or in New Zealanders. Stepwise removal of N-acetyl-neuraminic acid (NANA) with neuraminidase revealed that the most cathodal variant TF DShinnanyo found in a Japanese family was characterized by having only two NANA residues.

Gc types were examined in a total of 1,000 unrelated Japanese individuals from Western Japan. By isoelectric focusing the six common subtypes and several rare types were observed. In addition, a new variant with a mobility between the Gc 1S and 1C2 was identified in 2 individuals. A family investigation confirmed the inheritance of the corresponding allele Gc* 1C35.

PI phenotyping by separator isoelectric focusing (SIEF) was performed on a total of 1000 unrelated Japanese individuals from two different areas of Western Japan. The PI M1M4 subtype was observed together with the six common PI M subtypes. PI*M4 was confirmed to be present but rare in the Japanese. Several new PI variants were identified by comparison runs of each variant with previously reported genetic variants. The significance of treatment of serum with dithiothreitol (DTT) followed by iodacetic acid (IAC) in determination of PI variants is also described.